Relationship between Diabetes Mellitus and Serum Lathosterol and Campesterol Levels: The CACHE Study DM Analysis

Abstract

Aim: Risk of cardiovascular disease is increased in patients with diabetes mellitus (DM). Cholesterol metabolism (hepatic synthesis and intestinal absorption) is known to be associated with cardiovascular risk. Next, we examined the association of DM with cholesterol absorption/synthesis. Methods:The CACHE Consortium, which is comprised of 13 research groups in Japan possessing data of lathosterol (Latho, synthesis marker) and campesterol (Campe, absorption marker) measured by gas chromatography, compiled the clinical data using the REDCap system. Among the 3597 records, data from 2944 individuals were used for several analyses including this study.Results: This study analyzed data from eligible 2182 individuals including 830 patients with DM; 42.2% were female, median age was 59 years, and median HbA1c of patients with DM was 7.0%. There was no difference in Latho between DM and non-DM individuals. Campe and Campe/Latho ratio were significantly lower in DM individuals than in non-DM individuals. When the associations of glycemic control markers with these markers were analyzed with multivariable-adjusted regression model using restricted cubic splines, Campe and Campe/ Latho ratio showed inverse associations with glucose levels and HbA1c. However, Latho showed an inverted U-shaped association with plasma glucose, whereas Latho showed a U-shaped association with HbA1c. These associations remained even after excluding statin and/or ezetimibe users. Conclusion:We demonstrated that DM and hyperglycemia were independent factors for lower cholesterol absorption marker levels regardless of statin/ezetimibe use.

Association of Serum Oxysterols with Cholesterol Metabolism Markers and Clinical Factors in Patients with Coronary Artery Disease: A Covariance Structure Analysis

“…In addition, there is inconsistency as for the link between diabetes and cholesterol absorption in previous studies [35,36]. Matsumura et al reported that diabetes associated with lower cholesterol absorption independently [14]. However, we did not find a correlation between diabetes and cholesterol absorption or synthesis in this study.…”

“…Cholesterol synthesis can be assessed by measuring serum levels of lathosterol, a precursor of cholesterol [11]. Previous studies have indicated that various clinical factors, such as age, sex, obesity, hypertension, diabetes, renal dysfunction, and lipid-lowering medications, are associated with serum sterol levels [12][13][14][15][16]. Understanding the impact of these clinical factors on cholesterol metabolism and oxysterol levels in patients with CAD is of great importance.…”

Effects of Heat-Moisture-Treated High-Amylose Rice Flour on Body Weight, Lipid Metabolism, and Gut Microbiome Composition in Obese Rats

“…High levels of lathosterol can indicate increased cholesterol synthesis in the body [26]. In patients with T2D, the plasma level of campesterol is reported to be low [27], whereas a higher lathosterol profile is found [28].…”

“…High levels of lathosterol can indicate increased cholesterol synthesis in the body [ 26 ]. In patients with T2D, the plasma level of campesterol is reported to be low [ 27 ], whereas a higher lathosterol profile is found [ 28 ]. In the present study, we demonstrated that campesterol and lathosterol turnovers also exist in HFD-fed rats, while dietary HMT rice flour attenuated this fluctuation.…”

Long-term Efficacy and Safety of K-924 Pitavastatin/Ezetimibe Fixed-dose Combination in Patients with Hypercholesterolemia: A Phase III, Multi-center, Open-label Trial

“…These complementary actions may explain the favorable effects of statin-ezetimibe combination therapy. Diabetes mellitus has been associated with low levels of cholesterol absorption markers 27) . Considering the mechanism of ezetimibe, the levels of cholesterol absorption marker may affect the LDL-C lowering effect.…”